Follicle-stimulating hormone (FSH) is a gonadotropic hormone secreted by the anterior pituitary in all normal adult male and female mammals, and, in fact, probably in all vertebrates. In the male this hormone functions in the process of spermatogenesis, or sperm formation, by stimulating conversion of primary spermatocytes into secondary spermatocytes within the seminferous tubules. Without the action of FSH, sperm formation cannot proceed normally. In the female, FSH operates by initiating the growth of ovarian follicles and the enclosed ova during the female menstrual cycle. In conjunction with the action of a second hormone luteinizing hormone (LH), it promotes rapid follicular growth to the point of ovulation, or release of the ovum from the ovary. FSH thus plays an integral role in maintaining normal fertility in both males and females.
FSH, a glycoprotein, achieves its desired effect, as do other hormones, by interaction or binding with a receptor in the target cells of the appropriate organs, in this case, the ovaries or the testes. As it is currently understood, with protein or peptide hormones, the receptor is probably a membrane-localized macromolecule which recognizes the hormone in a particular way and activates the cell to initiate the appropriate biological response. Whatever the mechanism of action, it is known that interference with the binding of the hormone to the receptor will result in the prevention of the expression of the hormone's usual effect. Therefore, it is possible to control the action of FSH by preventing its binding to its receptor, thus interfering with normal fertility by disrupting the usual course of spermatogenesis or ovulation.
Substances which are capable of inhibiting the binding of FSH to its receptor have been reported from a number of sources. Such inhibitors have been found in bovine follicular fluid (Darga, N. S. and Reichert, L. E., Jr. Adv. Exp. Med. Biol.112: 383-388, 1977; Fletcher, P. W. et al., Mol. Cell. Endocrinol. 25: 303-315, 1982); human serum (Sanzo, M. S. and Reichert, L. E., Jr., J. Biol. Chem 257: 6033-6040, 1982) and seminal plasma (Dias, J. A. et al., J. Androl 5: 259-268, 1981). All of these substances are of low molecular weight (less than 1000), and neither the origin nor the identity of any of them is well-understood.
A new FSH-binding inhibitor has now been isolated. The inhibitor in question is readily distinguished from earlier known inhibitors by its much higher molecular weight (greater than 6,000), and a number of other chemical features. It is also unique in that it has been identified from a microbial source, the bacterium Serratia. This novel binding inhibitor has potential use as a contraceptive agent as well as a reagent in the study of FSH-receptor interactions and in purification of the FSH receptor.